RT Journal Article
SR Electronic
T1 The interaction landscape between transcription factors and the nucleosome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 240598
DO 10.1101/240598
A1 Zhu, Fangjie
A1 Farnung, Lucas
A1 Kaasinen, Eevi
A1 Sahu, Biswajyoti
A1 Yin, Yimeng
A1 Wei, Bei
A1 Dodonova, Svetlana
A1 Cramer, Patrick
A1 Taipale, Jussi
YR 2017
UL http://biorxiv.org/content/early/2017/12/29/240598.abstract
AB Nucleosomes cover most of the genome and are thought to be displaced by transcription factors (TFs) in regions that direct gene expression. However, the modes of interaction between TFs and nucleosomal DNA remain largely unknown. Here, we use nucleosome consecutive affinity-purification systematic evolution of ligands by exponential enrichment (NCAP-SELEX) to systematically explore interactions between the nucleosome and 220 TFs representing diverse structural families. Consistently with earlier observations, we find that the vast majority of TFs have less access to nucleosomal DNA than to free DNA. The motifs recovered from TFs bound to nucleosomal and free DNA are generally similar; however, steric hindrance and scaffolding by the nucleosome result in specific positioning and orientation of the motifs. Many TFs preferentially bind close to the end of nucleosomal DNA, or to periodic positions at its solvent-exposed side. TFs often also bind nucleosomal DNA in a particular orientation, because the nucleosome breaks the local rotational symmetry of DNA. Some TFs also specifically interact with DNA located at the dyad position where only one DNA gyre is wound, whereas other TFs prefer sites spanning two DNA gyres and bind specifically to each of them. Our work reveals striking differences in TF binding to free and nucleosomal DNA, and uncovers a rich interaction landscape between the TFs and the nucleosome.